Indian Pediatrics 1999;36:383-385

Correlation of Tomographic Liver Density with Serum Ferritin Levels in Multiply-Transfused Children with Thalassemia Major

Beta-thalassemia is one of the commonest genetic disorders afflicting Indians. Patients of beta thalassemia major are transfusion dependent and are consequently afflicted by iron overload. Serum ferritin level is the most commonly used parameter for judging the degree of iron overload. As liver is one of the organs affected by iron overload, a study was carried out to determine the relationship between tomographic ally determined liver density and serum ferritin levels.

Subjects and Methods

This prospective, cross-sectional analytical study was conducted in a large general hospital. Thirty consecutive patients with beta-thalassemia major aged 2-12 years were enrolled. Ten ml of fasting venous sample was collected and centrifuged immediately and plasma was stored frozen. Serum ferritin level in all the samples was determined at one time using radioimmunoassay (Diagnostic Products Corporation).

A CT scan of abdomen was performed within 24 hours of collection of samples using Siemens HiQ machine. Five readings of liver density were determined in each lobe avoiding biliary tract, portal vein and porta hepatis. An average of these ten readings was designated as the liver density for that patient.

Statistical analysis performed included Pearson's correlation coefficient and 't' test.

Results

There were thirteen boys among thirty patients enrolled in the study. The serum ferritin levels ranged from 1190 ng/ml to 15,000 ng/ ml. The average serum ferritin level was 4289.4 (±3514.1) ng/ml. The tomographic liver density measurements were normally distributed. The. mean tomographic liver density was 98.0±12.7 (range 72.3 - 119.8) Hounsefield units. The relationship between serum ferritin levels and tomographic liver density is depicted in Fig 1. The correlation coefficient between the variables was 0.67 (p <0.001). The relationship between serum ferIitin level (x) and tomographic liver density (y) could be expressed by the formula: y = 0.00247 x + 88.44.

Discussion

Patients of beta thalassemia major develop iron overload as a result of their inability to . excrete excessive iron they receive via multiple red-cell transfusions(1). In addition, incremental iron absorption from the gut contributes to the state of iron excess(2,3). This iron gets deposited in various tissues and organs producing morphological changes and functional derangements.

As an organ, the liver is likely to reflect iron overload in the body as it has abundant blood supply and is rich in reticulo-endothelial tissue which is the primary site of iron deposition( 4). Indeed, raised hepatic iron content and morphological changes such as parenchymal damage and hepatic fibrosis have been shown to reflect iron overload(5,6). However, these investigations require performance of the liver biopsy, which is an invasive procedure. Liver density could have been determined by using either MRI or CT scan. The latter was preferred as it is more widely available and is less expensive(5,6).

Similar to earlier observations(7), our ex- ploratory study also demonstrated significant linear correlation between tomographic liver density and serum ferritin level, a parameter commonly used to determine degree of iron

 

overload. Other investigators have shown that tomographic liver density correlates with histopathological changes in the liver(5) and hepatic iron content(5,6,8). The relationship demonstrated by us may have clinical impli- cations as well. It can be used to settle the issue of iron overload when erroneously low levels of serum ferritin are obtained, despite obvious signs of iron overload. In addition, earlier workers have found that tomographic liver density may be a better indicator of iron overload than serum ferritin levels in patients of thalassemia major on chelation therapy(9). This is because serum ferritin represents chelatable form of iron while liver density reflects both chelatable as well as non chelatable storage forms of iron in the body.

Acknowledgements

Authors thank Dr. (Mrs) P.M. Pai, Dean, Seth G.S. Medical College and K.E.M. Hospi- tal, Parel, Mumbai for permission to publish the article and Mr. M.B. Kulkarni for assistance in statistical analysis.

 

 References

1. Honig GR. Hemoglobin disorders. In: Textbook of Pediatrics, 15th edn. Eds. Nelson WE, Behrman RE, Kliegman RM, Arvin AM. Philadelphia, W.B. Saunders and Company, 1996; pp 1401-1404.

2. DeAlarcon PA, Donovan ME, Forbes GB, Landaw SA, Stockman JA. Iron absorption in thalassemia syndromes and its inhibition by tea. NEngl J Med 1979; 300: 5-8.

3. Bannerman RM, Callender ST, Hardisty RM, Smith S. Iron absorption in thalassemia. Br J HematoI1964; 10: 490-495.

4. Brittenham GM, Cohen AR, McLaren CE, Martin MB, Griffith PM, Nienhuis A W et a/. Hepatic iron stores and plasma ferritin concen- tration in patients with sickle cell anemia and thalassemia major. Am J Hematol 1993; 42: 81-85.

5. Mitnick JS, Mosnia MA, Megibow AJ, Karpatkin M, Feiner HD, Kutin N, et a/. CT in beta thalassemia, iron deposition in liver, spleen and lymph nodes. Am J Roentgenol 1981; 136: 1191-1194.

6. Long Jr JA. Doppman JL, Nienhuis A W, Mills SR. Computed tomographic analysis of beta thalassemia syndromes with hemochromatosis. Pathologic findings with clinical and laboratory correlations. J Comput Assist Tomogr 1980; 4: 159-165.

7. Babiker MA, Patel PI, Karrar ZA, Hafeez MH. Comparison between serum ferritin and computed tomographic densities of liver, spleen, , kidney and pancreas in beta thalassemia major. Scan I CHn Lab Invest 1987; 47: 715-718.

8. Houang MT, Arozena H. Skalicka A, Huehns ER, Shaw.DG. Correlation between computed tomographic values and liver iron content in thalassemia major with iron overload. Lancet 1979; I: 1322-1323.

9. Olivieri NF, Grisara D, Daneman A, Martin OJ, Rose Y, Freeman MH. Computed tomography scanning of liver to determine effi- cacy of iron chelation therapy of thalassemia major. J Pediatr 1989; 114: 427-430.